Cold snare biopsies in the ileum and colon for translational studies in inflammatory bowel disease: a feasibility study

Inflammatory bowel disease (IBD), including Crohn*s (CD) disease and ulcerative
colitis (UC), represents a significant public health challenge and has an
increasing incidence worldwide. IBD is characterized by chronic inflammation of
the gastrointestinal tract, leading to a wide range of symptoms. These include
abdominal pain, diarrhea, and weight loss. IBD is associated with a substantial
burden on patients* quality of life and on healthcare systems, making IBD an
area of intense scientific investigation and clinical interest.
In the search to unravel the pathophysiology of IBD, researchers have turned to
state-of-the-art technologies. For example, single-cell analysis and spatial
transcriptomics have revolutionized the ability to unravel the complex biology
of IBD. These technologies lead to the possibility to explore the
characteristics of single cells within the intestinal tissue, giving in-depth
insight in the disease*s pathophysiology.
However, although these technologies offer major opportunities for
understanding IBD at a molecular level, they expose a critical limitation in
the standard-of-care biopsy protocol used to collect intestinal samples.
Current biopsy techniques are considered safe but they are not tailored for
these advanced analytical methods. During the biopsy process, a considerable
number of cells are inadvertently lost and the architecture is damaged,
hindering the advanced research technologies. This cellular loss can lead to
suboptimal results, limiting the insights gained from these cutting-edge
techniques.
Therefore, a need arises for samples of improved quality that can align with
the requirements of the advanced research methods. Such improvements would
significantly enhance the ability to explore IBD comprehensively, shedding
light on its pathogenesis. Our study aims to address this by evaluating the
cold-snare biopsies, striving to provide high-quality tissue samples for the
advancement of IBD research.

Cold-snare technique
Cold snaring endoscopic mucosal resection (CS-EMR) is a minimally invasive
endoscopic procedure and is designed to remove and analyze abnormal or
pre-cancerous tissue from the gastrointestinal tract (2). CS-EMR combines
submucosal fluid injection and the use of a cold snare, a specialized cutting
instrument, which, as the name implies, does not rely on thermal energy for
tissue removal. Instead, it employs a snare-like mechanism to remove targeted
lesions with precision, often in a single session.
A lot of research has been performed to define the safety of CS-EMR in the
scope of polypectomy procedures. For example, a meta-analysis performed by
Ortigão and colleagues in 2021 analyzed the adverse event rate of CS-EMR of
polyps bigger than 10mm, reporting an adverse event range <1% (cumulative
n=577) (3). In addition, two randomized controlled trials that compared CS-EMR
to other polypectomy procedures reported post-procedural bleeding of 0% and
0.8% (n= 83; n=135) (4, 5).
Beyond polypectomy, there is a notable absence of data comparing sample quality
between cold-snare biopsies and the standard-of-care biopsy protocol.

Primary objective
The primary aim of this study is to assess and compare sample quality between
cold-snare biopsies and standard-of-care biopsies.

This prospective, single-center pilot study aims to evaluate sample quality of
cold-snare biopsies. The study includes three phases: rectal biopsy, colon
biopsy, and terminal ileum biopsy. After confirming the feasibility of the
cold-snare biopsy procedure in the rectum, the procedure will be extended to
the colon and terminal ileum. This phased approach is chosen, considering that
perforations in the rectum are typically less problematic due to the
retroperitoneal position, ensuring a methodical safety assessment. The study
has a 30-day follow-up period.

The intervention is endoscopic sampling of the rectum, colon and ileum. The
only deviation from routine clinical practice is the cold snare biopsy of the
specific segment.

Patients will not benefit from this study at the individual level.
Patients who participate will deliver standard-of-care biopsies and undergo a
cold-snare biopsy during routine endoscopy. The potential risk of participation
is low. Collection of the standard-of-care biopsies during endoscopy carries an
established risk (perforation or bleeding) of <1:10.000 procedures (endoscopy
with biopsies). In the current study, an additional cold-snare biopsy is taken.
Different studies have been performed to assess the safety of cold-snare
techniques and the risk of adverse events is considered to be low (<1%) in the
context of polypectomy procedures.
Most complications can be treated (coagulopathy/clipping) during the
colonoscopy. occasionally, an additional endoscopy has to be performed. In
seldom case the patient needs to be hospitalized for blood transfusion,
antibiotics or surgery. Patients are informed about all risks in the informed
consent form.